Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Adenomatous polyps or colorectal adenomas (CRAs) are the benign neoplastic precursors of CRCs, although most CRAs do not progress to CRC and not all colorectal polyps are adenomas. Recurrent CRAs develop at a rate of 10-15% per year in patients with previous CRAs and serve as endpoints in CRC chemoprevention trials. Considerable indirect evidence supports a chemopreventive role for selenium against CRC. The SELECT Trial will assess the effect of selenium, as L-selenomethionine, and vitamin E alone and in combination on the clinical incidence of prostate cancer in 35,584 now-randomized male subjects. Planned secondary objectives of SELECT include assessment of the effect of selenium and vitamin E on CRC incidence and CRC-free survival. The long-term objective of the current application is to address the CRC-related secondary objectives of the parent SELECT Trial. Specific Aims are to measure the effects of SELECT interventions on CRA prevalence in SELECT participants and to compare concurrently the effects of treatment with these interventions on CRC incidence and CRA prevalence in this study population. CRA prevalence will be determined from the procedure and histopathology reports of SELECT participants who undergo lower gasatrointestinal endoscopy (sigmoidoscopy or colonoscopy) and removal of colorectal polyps as part of their usual clinical care while in the trial. CRC incidence will be determined from a SELECT Trial protocol already in place to ascertain all non-prostate cancers diagnosed in participants while in the trial. The Principle Investigator (PI) of this application is also PI of the Colon Cancer Prevention Program Project (CCPPP), which includes a multi-center Phase III randomized selenium CRA recurrence trial. Existing SELECT Trial and CCPPP infrastructure will be utilized for all data collection and analyses, with consequent substantial cost savings. A unique aspect of the proposed study of colorectal neoplasia (CRAs and CRCs) in SELECT participants is the opportunity to investigate the effects of trial interventions on colorectal adenoma and cancer endpoints in the same (SELECT) study population. This study addresses a major unanswered question: Do agents that prevent recurrence of colorectal adenomas also prevent colorectal cancer? The question is addressed in the context of an already established clinical trial.